Spontaneous Diabetes Produced by Selective Breeding of Normal Wistar Rats

Gotō, Yoshio; Kakizaki, Masaei; Masaki, Naoyoshi

doi:10.2183/pjab1945.51.80

Cited by 254 publications

(200 citation statements)

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“…Our rats with spontaneous diabetes have characteristic diabetic features; glycosuria, glucose intolerance, reduced insulin secretion and other biochemical properties [3]. In both normal and diabetic animals, constant age-related increase in glomerular basement membrane thickness has been reported by only a few workers [8,9,10].…”

Section: Discussionmentioning

confidence: 67%

“…These rats show low insulin secretion, glycosuria and glucose intolerance. We have demonstrated previously a significant increase in glomerular basement membrane thickness in these diabetic rats at 24 weeks of age when compared with age-matched control rats [3]. However, no definitive study has been made of the age or stage of the disease when the increase of the capillary basement membrane thickness becomes apparent.…”

mentioning

confidence: 82%

“…Significant thickening of glomerular basement membrane was found in the diabetic rats at 12 weeks of age, while younger diabetic rats had no definite increase. The difference in basement membrane thickness between diabetic and normal control rats became larger with increasing age.Key words: Spontaneous diabetes rats, glomerular basement membrane, ageing, quantitative analysis.Rats with spontaneous diabetes can be obtained by selective breeding of animals with slightly abnormal glucose tolerance, selected from a population of normal Wistar rats [1,2]. These rats show low insulin secretion, glycosuria and glucose intolerance.…”

mentioning

confidence: 99%

“…All rats were given glucose tolerance tests (2 g/kg, orally). Blood glucose determination was made using a glucose oxidase method, as described elsewhere [1,2]. The rats were given water and standard rat chow (Oriental MF) libitum until sacrifice.…”

mentioning

confidence: 99%

“…Rats with spontaneous diabetes can be obtained by selective breeding of animals with slightly abnormal glucose tolerance, selected from a population of normal Wistar rats [1,2]. These rats show low insulin secretion, glycosuria and glucose intolerance.…”

mentioning

confidence: 99%

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Thickening of glomerular basement membrane in spontaneously diabetic rats

et al. 1978

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Summary. The glomerular basement membrane of spontaneously diabetic rats was investigated by quantitative analysis using electron microscopy, with special reference to the effect of ageing. Constant agerelated increase in the width of basement membrane was ascertained both in diabetic and control rats, and the mean values of basement membrane thickness were always higher in the spontaneously diabetic rats than in normal control rats. Significant thickening of glomerular basement membrane was found in the diabetic rats at 12 weeks of age, while younger diabetic rats had no definite increase. The difference in basement membrane thickness between diabetic and normal control rats became larger with increasing age.Key words: Spontaneous diabetes rats, glomerular basement membrane, ageing, quantitative analysis.Rats with spontaneous diabetes can be obtained by selective breeding of animals with slightly abnormal glucose tolerance, selected from a population of normal Wistar rats [1,2]. These rats show low insulin secretion, glycosuria and glucose intolerance. We have demonstrated previously a significant increase in glomerular basement membrane thickness in these diabetic rats at 24 weeks of age when compared with age-matched control rats [3]. However, no definitive study has been made of the age or stage of the disease when the increase of the capillary basement membrane thickness becomes apparent. The present study was undertaken to clarify these points. Materials and MethodsTwenty two spontaneously diabetic rats and 36 normal rats of male Wistar strain were used. Diabetic rats were divided into six groups; three 8 week-old, three 12 week-old, two 16 week-old, six 24 week-old, four 25 to 28 week-old and four 29 to 32 week-old. Nine groups of age-matched control rats consisted of animals from four to 36 weeks of age at four weeks intervals. Each control group consisted of four rats. All rats were given glucose tolerance tests (2 g/kg, orally). Blood glucose determination was made using a glucose oxidase method, as described elsewhere [1,2]. The rats were given water and standard rat chow (Oriental MF) libitum until sacrifice. Detailed laboratory data and glomerular basement membrane thickness of normal control rats have been published in our previous report [4].Tissue specimens for electron microscopy were prepared as follows: after an overnight fast, rats were killed by decapitation. The abdominal cavity was opened, and the left renal cortex cut into small pieces. The small specimens of renal tissue were immersed in 4 g/100 ml glutaraldehyde in 0.15 mol/1 phosphate buffer, pH 7.4, for 11/2 hrs and rinsed in the same buffer overnight. After postfixation in 1 g/100 ml osmium tetroxide, specimens were dehydrated through an ascending series of ethanol. They were then embedded in Maraglas 655 and polymerized at 60 ~ C for 48 hrs [5]. Ultrathin sections were obtained by Porter-Blum MT 2B ultramicrotome and stained with uranyl acetate and lead citrate [6]. Electron micrographs were obtained using a Hitachi HU 12S electron ...

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Section: Discussionmentioning

confidence: 67%

mentioning

confidence: 82%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Thickening of glomerular basement membrane in spontaneously diabetic rats

et al. 1978

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Effect of dehydroepiandrosterone in hereditarily diabetic rats

Ladrière¹,

Laghmich²,

Malaisse‐Lagae³

et al. 1997

Cell Biochem. Funct.

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Goto-Kakizaki rats (GK rats) were given access for 4 weeks to a diet enriched with dehydroepiandrosterone (DHEA, 0.2 per cent, w/w). The incorporation of DHEA in the food failed to affect significantly body growth, plasma D-glucose and insulin concentrations, pancreatic islet insulin content or the activity of both mitochondrial glycerophosphate dehydrogenase (mGDH) and NADP-malate dehydrogenase (malic enzyme) in islet homogenates. DHEA however, increased the activity of mGDH and, at least in male rates, that of the malic enzyme also in the liver. It lowered the abnormally high basal insulin release otherwise found in the islets from diabetic rats, and, as judged from the ratio of insulin output at 16.7 mM/2.8 mM D-glucose, improved the cell responsiveness to the hexose. This coincided with a decreased plasma insulin/D-glucose ratio, suggesting that the major effect of DHEA was to increase the sensitivity to insulin of extrapancreatic targets, thus resulting in a secondary improvement of cell secretory behaviour.

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Effects of long-term treatment with α-glucosidase inhibitor on the peripheral nerve function and structure in Goto-Kakizaki rats: a genetic model for Type 2 diabetes

Wada

Koyama

Mizukami

et al. 1999

Diabetes Metab. Res. Rev.

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Background Continuous hyperglycemia is implicated in the pathogenesis of chronic diabetic complications. It is not well known, however, how and to what extent the development of neuropathy is inhibited by blood glucose control in subjects with Type 2 diabetes. We investigated therefore the effects of an α‐glucosidase inhibitor (voglibose; Vg) on neuropathic changes in diabetic Goto‐Kakizaki (GK) rats, a genetic model for Type 2 diabetes. Methods Twelve week‐old male GK rats were given a diet containing Vg (50 ppm) for 24 weeks and monitored for blood glucose, glycated hemoglobin, motor nerve conduction velocity (MNCV). At the end of the administration period (Na+, K+)‐ATPase activity and the structure of the peripheral nerves were examined. Age‐ and sex‐matched normal Wistar rats were treated similarly and served as controls. Results GK rats showed fasting hyperglycemia after 8 weeks of age, and Vg treatment significantly lowered levels of blood glucose and glycated hemoglobin. Slowing of MNCV to 80% of normal control levels was detected in GK rats. Vg treatment inhibited this delay by 24% at 24 weeks and 57% at 36 weeks of age. Nerve (Na+, K+)‐ATPase activity was reduced to 80% of normal control levels in GK rats and was restored by Vg treatment. Teased fiber studies revealed a higher incidence of fibers with paranodal, segmental demyelination and axonal degeneration in GK rats. Vg treatment significantly inhibited the development of these nerve‐fiber abnormalities. Conclusions Lowering of high blood glucose levels achieved by the use of Vg in GK rats improved MNCV and demyelinative nerve changes with restoration of (Na+, K+)‐ATPase activity. Copyright © 1999 John Wiley & Sons, Ltd.

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Spontaneous Diabetes Produced by Selective Breeding of Normal Wistar Rats

Cited by 254 publications

References 6 publications

Thickening of glomerular basement membrane in spontaneously diabetic rats

Thickening of glomerular basement membrane in spontaneously diabetic rats

Effect of dehydroepiandrosterone in hereditarily diabetic rats

Effects of long-term treatment with α-glucosidase inhibitor on the peripheral nerve function and structure in Goto-Kakizaki rats: a genetic model for Type 2 diabetes

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